The cerebral edema associated with malignant brain tumors causes neurologic deficits and increased intracranial pressure, and contributes to the morbidity and mortality of the neoplasm. We have determined that the conditioned medium of glioblastoma-derived cell cultures contains a substance capable of increasing the vascular permeability in a bioassay which measures the induction of capillary permeability in normal skin. Partial purification and biochemical characterization of this vascular permeability factor (VPF) suggest that it is a heparin binding cationic polypeptide which is distinct from other known inducers of vascular permeability such as histamine, prostaglandins, leukotrienes, and plasminogen activator. Although the mechanisms of action of VPF remains unknown, the ability of VPF-containing conditioned medium to alter calcium flux in cultured endothelial cells suggests that VPF exerts its effect through a direct action on endothelial cells.